Progress and Challenges in Implementing the Research on ESKAPE Pathogens

2010 ◽  
Vol 31 (S1) ◽  
pp. S7-S10 ◽  
Author(s):  
Louis B. Rice
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Optimal Strategies ◽  
Resistance Mechanisms ◽  
Antimicrobial Use ◽  
Individual Resistance ◽  
Population Science ◽  
Eskape Pathogens ◽  
Modern Hospital ◽  
The Impact

The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, andEnterobacterspecies) are responsible for a substantial percentage of nosocomial infections in the modern hospital and represent the vast majority of isolates whose resistance to antimicrobial agents presents serious therapeutic dilemmas for physicians. Over the years, improved molecular biology techniques have led to detailed information about individual resistance mechanisms in all these pathogens. However, there remains a lack of compelling data on the interplay between resistance mechanisms and between the bacteria themselves. In addition, data on the impact of clinical interventions to decrease the prevalence of resistance are also lacking. The difficulty in identifying novel antimicrobial agents with reliable activity against these pathogens argues for an augmentation of research in the basic and population science of resistance, as well as careful studies to identify optimal strategies for infection control and antimicrobial use.

scholarly journals Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Sirijan Santajit ◽  
Nitaya Indrawattana
Keyword(s):  
Public Health ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Global Public Health ◽  
Drug Usage ◽  
Inappropriate Use ◽  
Public Health Challenges ◽  
Eskape Pathogens

The ESKAPE pathogens (Enterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa, andEnterobacterspecies) are the leading cause of nosocomial infections throughout the world. Most of them are multidrug resistant isolates, which is one of the greatest challenges in clinical practice. Multidrug resistance is amongst the top three threats to global public health and is usually caused by excessive drug usage or prescription, inappropriate use of antimicrobials, and substandard pharmaceuticals. Understanding the resistance mechanisms of these bacteria is crucial for the development of novel antimicrobial agents or other alternative tools to combat these public health challenges. Greater mechanistic understanding would also aid in the prediction of underlying or even unknown mechanisms of resistance, which could be applied to other emerging multidrug resistant pathogens. In this review, we summarize the known antimicrobial resistance mechanisms of ESKAPE pathogens.

scholarly journals The Principles, Mechanisms, and Benefits of Unconventional Agents in the Treatment of Biofilm Infection

2020 ◽  
Vol 13 (10) ◽  
pp. 299
Author(s):  
Jasminka Talapko ◽  
Ivana Škrlec
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Treatment Strategies ◽  
Cationic Peptides ◽  
Bacterial Cells ◽  
Infectious Agents ◽  
Severe Infections ◽  
Eskape Pathogens ◽  
Interdependent Relationships ◽  
Biofilm Infection

Today, researchers are looking at new ways to treat severe infections caused by resistance to standard antibiotic therapy. This is quite challenging due to the complex and interdependent relationships involved: the cause of infection–the patient–antimicrobial agents. The sessile biofilm form is essential in research to reduce resistance to very severe infections (such as ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanni, Pseudomonas aeruginosa, and Enterobacter spp). The purpose of this study is to elucidate the mechanisms of the occurrence, maintenance, and suppression of biofilm infections. One form of biofilm suppression is the efficient action of natural antagonists of bacteria—bacteriophages. Bacteriophages effectively penetrate the biofilm’s causative cells. They infect those bacterial cells and either destroy them or prevent the infection spreading. In this process, bacteriophages are specific, relatively easy to apply, and harmless to the patient. Antimicrobial peptides (AMPs) support the mechanisms of bacteriophages’ action. AMPs could also attack and destroy infectious agents on their own (even on biofilm). AMPs are simple, universal peptide molecules, mainly cationic peptides. Additional AMP research could help develop even more effective treatments of biofilm (bacteriophages, antibiotics, AMPs, nanoparticles). Here, we review recent unconventional agents, such as bacteriophages and AMPs, used for eradication of biofilm, providing an overview of potentially new biofilm treatment strategies.

scholarly journals Impact of an Antimicrobial Utilization Program on Antimicrobial Use at a Large Teaching Hospital A Randomized Controlled Trial

2009 ◽  
Vol 30 (10) ◽  
pp. 931-938 ◽  
Author(s):  
Bernard C. Camins ◽  
Mark D. King ◽  
Jane B. Wells ◽  
Heidi L. Googe ◽  
Manish Patel ◽  
...  
Keyword(s):  
Internal Medicine ◽  
Teaching Hospital ◽  
Antimicrobial Agents ◽  
Intervention Group ◽  
Control Group ◽  
Antimicrobial Use ◽  
Randomized Controlled ◽  
Antimicrobial Usage ◽  
Antimicrobial Utilization ◽  
The Impact

Background.Multidisciplinary antimicrobial utilization teams (AUTs) have been proposed as a mechanism for improving antimicrobial use, but data on their efficacy remain limited.Objective.To determine the impact of an AUT on antimicrobial use at a teaching hospital.Design.Randomized controlled intervention trial.Setting.A 953-bed, public, university-affiliated, urban teaching hospital.Patients.Patients who were given selected antimicrobial agents (piperacillin-tazobactam, levofloxacin, or vancomycin) by internal medicine ward teams.Intervention.Twelve internal medicine teams were randomly assigned monthly: 6 teams to an intervention group (academic detailing by the AUT) and 6 teams to a control group that was given indication-based guidelines for prescription of broad-spectrum antimicrobials (standard of care), during a 10-month study period.Measurements.Proportion of appropriate empirical, definitive (therapeutic), and end (overall) antimicrobial usage.Results.A total of 784 new prescriptions of piperacillin-tazobactam, levofloxacin, and vancomycin were reviewed. The proportion of antimicrobial prescriptions written by the intervention teams that was considered to be appropriate was significantly higher than the proportion of antimicrobial prescriptions written by the control teams that was considered to be appropriate: 82% versus 73% for empirical (risk ratio [RR], 1.14; 95% confidence interval [CI], 1.04-1.24), 82% versus 43% for definitive (RR, 1.89; 95% CI, 1.53-2.33), and 94% versus 70% for end antimicrobial usage (RR, 1.34; 95% CI, 1.25-1.43). In multivariate analysis, teams that received feedback from the AUT alone (adjusted RR, 1.37; 95% CI, 1.27-1.48) or from both the AUT and the infectious diseases consultation service (adjusted RR, 2.28; 95% CI, 1.64-3.19) were significantiy more likely to prescribe end antimicrobial usage appropriately, compared with control teams.Conclusions.A multidisciplinary AUT that provides feedback to prescribing physicians was an effective method in improving antimicrobial use.Trial Registration.ClinicalTrials.gov identifier: NCT00552838.

scholarly journals New Role of the Disulfide Stress Effector YjbH in β-Lactam Susceptibility of Staphylococcus aureus

2011 ◽  
Vol 55 (12) ◽  
pp. 5452-5458 ◽  
Author(s):  
Nadine Göhring ◽  
Iris Fedtke ◽  
Guoqing Xia ◽  
Ana M. Jorge ◽  
Mariana G. Pinho ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Stress Responses ◽  
Oxidative Burst ◽  
Resistance Mechanisms ◽  
Phenotypic Change ◽  
Content Type ◽  
Regulatory Pathways ◽  
Moderate Resistance ◽  
The Impact

ABSTRACTStaphylococcus aureusis exposed to multiple antimicrobial compounds, including oxidative burst products and antibiotics. The various mechanisms and regulatory pathways governing susceptibility or resistance are complex and only superficially understood.Bacillus subtilisrecently has been shown to control disulfide stress responses by the thioredoxin-related YjbH protein, which binds to the transcriptional regulator Spx and controls its degradation via the proteasome-like ClpXP protease. We show that theS. aureusYjbH homolog has a role in susceptibility to the disulfide stress-inducing agent diamide that is similar to that inB. subtilis, and we demonstrate that the four cysteine residues in YjbH are required for this activity. In addition, the inactivation of YjbH led to moderate resistance to oxacillin and other β-lactam antibiotics, and this phenotypic change was associated with higher penicillin-binding protein 4 levels and increased peptidoglycan cross-linking. Of note, the impact of YjbH on β-lactam susceptibility still was observed when the four cysteines of YjbH were mutated, indicating that the roles of YjbH in disulfide stress and β-lactam resistance rely on different types of interactions. These data suggest that the ClpXP adaptor YjbH has more target proteins than previously thought, and that oxidative burst and β-lactam resistance mechanisms ofS. aureusare closely linked.

scholarly journals Antibiotic susceptibility of Staphylococcus aureus with different degrees of biofilm formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hyo-Jung Shin ◽  
Sungtae Yang ◽  
Yong Lim
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Resistance Mechanisms ◽  
Minimal Bactericidal Concentration ◽  
Chronic Infections ◽  
Planktonic Bacteria ◽  
Growth Modes ◽  
Biofilm Bacteria ◽  
Biofilm Development

AbstractStaphylococcus aureus is one of the most common pathogens in biofilm-associated chronic infections. S. aureus living within biofilms evades the host immune response and is more resistant to antibiotics than planktonic bacteria. In this study, we generated S. aureus with low and high levels of biofilm formation using the rbf (regulator of biofilm formation) gene and performed a BioTimer assay to determine the minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of various types of antibiotics. We showed that biofilm formation by S. aureus had a greater effect on MBC than MIC, probably due to the different growth modes between planktonic and biofilm bacteria. Importantly, we found that the MBC for biofilm S. aureus was much higher than that for planktonic cells, but there was little difference in MBC between low and high levels of biofilm formation. These results suggest that once the biofilm is formed, the bactericidal activity of antibiotics is significantly reduced, regardless of the degree of S. aureus biofilm formation. We propose that S. aureus strains with varying degrees of biofilm formation may be useful for evaluating the anti-biofilm activity of antimicrobial agents and understanding antibiotic resistance mechanisms by biofilm development.

Antimicrobial Use Prior to the Acquisition of Multiresistant Bacteria

2002 ◽  
Vol 23 (3) ◽  
pp. 155-158 ◽  
Author(s):  
Matthieu Eveillard ◽  
Jean-Luc Schmit ◽  
François Eb
Keyword(s):  
Staphylococcus Aureus ◽  
Prospective Study ◽  
Clavulanic Acid ◽  
Antimicrobial Therapy ◽  
Antimicrobial Agents ◽  
Antimicrobial Use ◽  
Third Generation ◽  
Multiresistant Bacteria ◽  
Amoxicillin Clavulanic Acid ◽  
Third Generation Cephalosporins

AbstractWe assessed whether patients who acquired methicillin-resistantStaphylococcus aureus(MRSA) had less exposure to antimicrobial agents than did those who acquired Enterobacteriaceae that produced extended-spectrum β-lactamase (ESβL). In a 6-month, prospective study, ESβL carriers had received antimicrobial therapy more often than had MRSA carriers. Amoxicillin-clavulanic acid, fluoroquinolones, and third-generation cephalosporins, especially ceftazidime, had been prescribed more often for ESβL carriers than for MRSA carriers.

scholarly journals COMMUNITY-ACQUIRED PNEUMONIA IN INFECTIOUS HOSPITAL PATIENTS: THE DEVELOPMENT OF RESISTANCE TO ANTIMICROBIALS

2018 ◽  
Vol 23 (3) ◽  
pp. 108-113
Author(s):  
Marina G. Avdeeva ◽  
G. V. Shubina ◽  
A. A. Ganzha ◽  
E. V. Zhuravleva
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Resistance Mechanisms ◽  
Community Acquired Pneumonia ◽  
Diffusion Method ◽  
Individual Risk ◽  
Beta Lactam ◽  
Local Data ◽  
Antimicrobial Drugs

The aim of the work was to study the structure, level and dynamics of resistance to antimicrobial drugs of the most common types of microorganisms in patients with community-acquired pneumonia (CAP) in the Krasnodar Territory, on the example of patients treated in a regional specialized infectious hospital for the period 2015-2017. Materials and methods. The results of bacteriological tests of expectoration, including 523 positive strains of microorganisms, are analyzed. The analysis does not include strains with hospital multidrug resistance. A bacterioscopy with Gram stain and sputum seeding on plate-like artificial nutrient media were carried out. Identification of the pathogen was performed by mass spectrometry using MALDI-TOF technology (Microflex LT, Bruker, Germany), phenotypically identified resistance mechanisms were confirmed on the automatic analyzer Vitek II Compact (BioMérieux, France). The sensitivity to antimicrobials was determined by the disc-diffusion method in the Müller-Hinton medium, using the disks by Bio-Rad, France. The antibioticogram was analyzed on the apparatus “Adagio” (Bio-Rad, France). Results. In the etiologic structure of community-acquired pneumonia, Streptoccocus pneumonia prevails in patients hospitalized in an infectious hospital in the Krasnodar Territory, which is determined in 73.56% of confirmed cases, which is twice as high as an average in Russia. Staphylococcus aureus was determined in 9.04% of casesd, with fluctuations in different years from 3.8% to 12.1%. Klebsiella pneumoniae was found in 4.61%, with variations from 1.7% to 9.3%. Pseudomonas aeruginosa was registered in 4.6%, altered from 1.3% to 7.8%. Other microorganisms were represented with Enterobacteriaceae family, 8.2% of the cases. The resistance of wild strains of microorganisms isolated at CAP to a number of antimicrobial agents has been established. A number of negative trends were noted: the emergence of pneumococcal strains resistant to beta-lactam antimicrobial drugs (benzylpenicillin MIC < 2μg); an increase in the resistance of pneumococci to macrolides, tetracyclines, sulfonamides. There is a high percentage of Staphylococcus aureus (80%) producing penicillinase, and an increase in their resistance to macrolides. A high level of Pseudomonas aeruginosa resistance to 3-rd and 4-th generation cephalosporins is noted. Conclusion. The obtained data determine the need for further monitoring of regional resistance of microorganisms, which will allow both adequate start therapy and the possibility of its timely correction. In the practical work of a doctor, it is important not only to be guided by local data on the resistance of microorganisms to antimicrobial drugs, but also to analyze the possible causes of its occurrence with the establishment of individual risk factors.

scholarly journals Evolution of resistance mechanisms and biological characteristics of rifampicin-resistant Staphylococcus aureus strains selected in vitro

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chong Wang ◽  
Renchi Fang ◽  
Beibei Zhou ◽  
Xuebin Tian ◽  
Xiucai Zhang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Galleria Mellonella ◽  
Resistance Mechanisms ◽  
Fitness Cost ◽  
Rifampicin Resistance ◽  
Infection Model ◽  
Resistance Mutations ◽  
Evolution Of Resistance ◽  
The Impact

Abstract Background We aimed to determine the evolutionary pathways of rifampicin resistance in Staphylococcus aureus, and the impact of resistance mutations in the rpoB gene on fitness. Methods Three clinical strains and one reference strain were used to select for rifampicin-resistant S. aureus variants. The mutations responsible for rifampicin resistance in all of the selected isolates in vitro were investigated by polymerase chain reaction (PCR) and DNA sequencing. To compare the fitness cost of rpoB mutations against their corresponding original isolates, we performed bacterial growth curve assays, static biofilm assays, in vitro competition experiments and an infection model of Galleria mellonella larvae. Results We obtained four rifampicin-resistant S. aureus isolates that showed high levels of resistance to rifampicin with a minimal inhibitory concentration (MIC) of 128 mg/L, and all isolates had a mutation at position 481 (H481F/Y) in RpoB. A broth microdilution assay indicated that mutation of H481F/Y did not affect susceptibility to common antibacterial drugs but slightly increased the vancomycin MIC. To identify the pathways involved in the development of rifampicin resistance, 32 variants (eight mutants for each strain) and four original isolates were selected for gene sequencing. Different generations of isolates were found to harbor various mutations sites. Compared with the corresponding original isolates, an in vitro fitness assay of the variant isolates showed that growth and virulence were reduced, with a statistically significantly decreased fitness, whereas the capacity for biofilm formation was elevated. Conclusions Our findings suggested that the acquisition of rifampicin resistance in S. aureus was dynamic and was associated with a significant fitness cost.

scholarly journals Convergent Adaptation in the Dominant Global Hospital Clone ST239 of Methicillin-Resistant Staphylococcus aureus

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Sarah L. Baines ◽  
Kathryn E. Holt ◽  
Mark B. Schultz ◽  
Torsten Seemann ◽  
Brian O. Howden ◽  
...  
Keyword(s):  
Health Care ◽  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Health Care Environment ◽  
Methicillin Resistant ◽  
Content Type ◽  
Public Health Burden ◽  
Evolutionary Response ◽  
The Impact

ABSTRACTInfections caused by highly successful clones of hospital-associated methicillin-resistantStaphylococcus aureus(HA-MRSA) are a major public health burden. The globally dominant sequence type 239 (ST239) HA-MRSA clone has persisted in the health care setting for decades, but the basis of its success has not been identified. Taking a collection of 123 ST239 isolates spanning 32 years, we have used population-based functional genomics to investigate the evolution of this highly persistent and successful clone. Phylogenetic reconstruction and population modeling uncovered a previously unrecognized distinct clade of ST239 that was introduced into Australia from Asia and has perpetuated the epidemic in this region. Functional analysis demonstrated attenuated virulence and enhanced resistance to last-line antimicrobials, the result of two different phenomena, adaptive evolution within the original Australian ST239 clade and the introduction of a new clade displaying shifts in both phenotypes. The genetic diversity between the clades allowed us to employ genome-wide association testing and identify mutations in other essential regulatory systems, includingwalKR, that significantly associate with and may explain these key phenotypes. The phenotypic convergence of two independently evolving ST239 clades highlights the very strong selective pressures acting on HA-MRSA, showing that hospital environments have favored the accumulation of mutations in essential MRSA genes that increase resistance to antimicrobials, attenuate virulence, and promote persistence in the health care environment. Combinations of comparative genomics and careful phenotypic measurements of longitudinal collections of clinical isolates are giving us the knowledge to intelligently address the impact of current and future antibiotic usage policies and practices on hospital pathogens globally.IMPORTANCEMethicillin-resistantStaphylococcus aureus(MRSA) is responsible for innumerable drug-resistant health care-associated infections globally. This study, the first to investigate the evolutionary response of hospital-associated MRSA (HA-MRSA) over many decades, demonstrates how MRSA can persist in a region through the reintroduction of a previously unrecognized distinct clade. This study also demonstrates the crucial adaptive responses of HA-MRSA to the highly selective environment of the health care system, the evolution of MRSA isolates to even higher levels of antibiotic resistance at the cost of attenuated virulence. However,in vivopersistence is maintained, resulting in a clone of HA-MRSA able to resist almost all antimicrobial agents and still cause invasive disease in the heavily compromised hosts found in modern health care settings.

Topical Therapy for Methicillin-Resistant Staphylococcus aureus Colonization Impact on Infection Risk

2009 ◽  
Vol 30 (7) ◽  
pp. 623-632 ◽  
Author(s):  
Ari Robicsek ◽  
Jennifer L. Beaumont ◽  
Richard B. Thomson ◽  
Geetha Govindarajan ◽  
Lance R. Peterson
Keyword(s):  
Risk Factors ◽  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Topical Therapy ◽  
Care Facility ◽  
Term Care ◽  
Methicillin Resistant ◽  
Mrsa Infection ◽  
Independent Risk Factors ◽  
The Impact

Objective.We evaluated the usefulness of topical decolonization therapy for reducing the risk of methicillin-resistant Staphylococcus aureus (MRSA) infection among MRSA-colonized inpatients.Design.Retrospective cohort study.Setting and Intervention.Three hospitals with universal surveillance for MRSA; at their physician's discretion, colonized patients could be treated with a 5-day course of nasal mupirocin calcium 2%, twice daily, plus Chlorhexidine gluconate 4% every second day.Patients and Methods.MRSA carriers were later retested for colonization (407 subjects; study 1) or followed up for development of MRSA infection (933 subjects; study 2). Multivariable methods were used to determine the impact of decolonization therapy on the risks of sustained colonization (in study 1) and MRSA infection (in study 2).Results.Independent risk factors for sustained colonization included residence in a long-term care facility (odds ratio [OR], 1.8 [95% confidence interval {CI}, 1.1–3.2]) and a pressure ulcer (OR, 2.3 195% CI, 1.2–4.4]). Mupirocin at any dose decreased this risk, particularly during the 30-60-day period after therapy; mupirocin resistance increased this risk (OR, 4.1 [95% CI, 1.6–10.7]). Over a median follow-up duration of 269 days, 69 (7.4%) of 933 patients developed infection. Independent risk factors for infection were length of stay (hazard ratio [HR], 1.2 per 5 additional days [95% CI, 1.0–1.4]), chronic lung disease (HR, 1.7 [95% CI, 1.0–2.8]), and receipt of non-MRSA-active systemic antimicrobial agents (HR, 1.8 [95% CI, 1.1–3.1]). Receipt of mupirocin did not affect the risk of infection, although there was a trend toward delayed infection among patients receiving mupirocin (median time to infection, 50 vs 15.5 days; P = .06).Conclusions.Mupirocin-based decolonization therapy temporarily reduced the risk of continued colonization but did not decrease the risk of subsequent infection.

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